Heparin-induced thrombocytopenia (HIT) type II is an immune-mediated disorder. The autoantibodies formed target which neoantigen?
- A Von Willebrand factor multimers released by heparin-activated endothelium
- B Heparin-antithrombin III complex exposing a cryptic antigen on antithrombin
- C Glycoprotein IIb/IIIa (αIIbβ3) neoepitope exposed by heparin-mediated platelet activation
- D Platelet factor 4 (PF4) / heparin complex, forming IgG antibodies that activate platelets via FcγRIIA ✓
Explanation
In HIT type II, heparin binds to platelet factor 4 (PF4, CXCL4), a positively charged protein released from platelet alpha-granules. This heparin-PF4 complex induces a conformational change in PF4, exposing a neoepitope not present on free PF4. In susceptible individuals, IgG antibodies form against this PF4/heparin complex. These IgG antibodies then cross-link Fc-gamma receptor IIA (FcγRIIA, CD32) on platelet surfaces, causing massive platelet activation, aggregation, and release, resulting in thrombocytopenia and paradoxical thrombosis. Argatroban or bivalirudin (direct thrombin inhibitors) are used as alternative anticoagulants in HIT since heparins must be stopped completely.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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